21st century biomedical research is being driven by the need for new drugs and procedures for solving humankind's most persistent and difficult medical problems. This research critically depends upon computer- intensive structure-based approaches to understand biological macromolecules and supramolecular assemblies in atomic detail. Progress is accelerating at a dizzying rate, and there is a critical need to promote integrative approaches driven by computational structural biologists. To help meet this challenge, our goal is to provide an environment for broadening the thinking of senior scientists, and, more important, to create a new diverse generation of theory-driven integrative scientists studying the structure and dynamics of proteins, membranes, lipoproteins, RNA and ribosomes. In this dual PI grant application, Jere Segrest (UAB) and Steve Harvey (Georgia Tech) are seeking 3 years support for an ongoing annual symposium entitled, Frontiers in Macromolecular Simulations that was held for the 6th time in the fall of 2009. For the past four years, the site of this symposium has alternated between UAB in Birmingham, AL and Georgia Tech in Atlanta, GA. The objective of our dual PI grant application is to hold a series of three annual conferences dedicated to fast breaking research in structure and dynamics of membranes, lipoproteins, proteins, RNA and ribosomes. Presentations at the proposed symposia will focus on theory-driven physics-based molecular modeling, simulations and experimentation. Biological research is increasingly multidisciplinary, and many experimental groups now routinely use sophisticated computational tools in their work. Our aim is to provide a venue in which application-oriented computational structural biologists will be exposed to the latest methodological advances (and provide feedback on suggested improvements), and in which experimentalists will have the opportunity to stimulate the thinking of computational biologists, both those who are primarily interested in applications, and those whose primary interest is the development of algorithms. We propose to hold the first of the three planned annual conferences for three days in March 30-April 1, 2011 at the Grand Hotel Marriott, Point Clear, Alabama. Approximately two-thirds of the platform speaker's slots will be reserved for membranes, lipoproteins and proteins and one-third for RNA and ribosomes. The two keynote speakers, Harry Gray, Professor of Chemistry, California Institute of Technology and Rachel Green, Professor of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, have agreed to join the two PIs in the organizing committee for the first conference. In addition to the keynote speakers, nine platform speakers, four women and one minority, have committed for the 2011 symposium. The second in the planned series of three conferences will be held off the Georgia Tech campus in the spring of 2012 at a still to be determined site in the State of Georgia. The final conference in the series will be held in the spring of 2013 at a neutral to be determined site in a third state, not necessarily in the Southeast. PUBLIC HEALTH RELEVANCE: The use of computers by molecular scientists to discover new drugs is increasing at a dizzying pace. To create a new generation of computer-savvy biomedical researchers, we propose three yearly conferences dedicated to a vigorous exchange of ideas between scientists on futuristic ways to incorporate computers into drug- discovery.